Pediatric Anesthesia ISSN 1155-5645
REVIEW ARTICLE
Dexmedetomidine vs midazolam as preanesthetic medication in children: a meta-analysis of randomized controlled trials Laura Pasin1, Daniela Febres1, Valentina Testa1, Elena Frati1, Giovanni Borghi1, Giovanni Landoni1,2 & Alberto Zangrillo1,2 1 Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy 2 Vita-Salute San Raffaele University, Milan, Italy
What’s known
• Premedication reduces perioperative anxiety in children. What this article adds
• Dexmedetomidine is more effective than midazolam in decreasing preoperative anxiety, postoperative agitation, and in providing more effective postoperative analgesia.
Implications
• Dexmedetomidine is an effective alternate sedative for pre medication in children
Keywords anesthesia-pediatric; dexmedetomidine; meta-analysis; midazolam; premedication; children Correspondence Dott. Laura Pasin, Department of Anaesthesia and Intensive Care, San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy Email: [email protected] Section Editor: Andrew Davidson Accepted 30 October 2014 doi:10.1111/pan.12587
468
Summary Introduction: The preoperative period is a stressing occurrence for most people undergoing surgery, in particular children. Approximately 50–75% of children undergoing surgery develop anxiety which is associated with distress on emergence from anesthesia and with later postoperative behavioral problems. Premedication, commonly performed with benzodiazepines, reduces preoperative anxiety, facilitates separation from parents, and promotes acceptance of mask induction. Dexmedetomidine is a highly selective a2-agonist with sedative and analgesic properties. A meta-analysis of all randomized controlled trials (RCTs) on dexmedetomidine versus midazolam was performed to evaluate its efficacy in improving perioperative sedation and analgesia, and in reducing postoperative agitation when used as a preanesthetic medication in children. Methods: Studies were independently searched in PubMed, BioMedCentral, Embase, and the Cochrane Central Register of clinical trials and updated on August 15th, 2014. Primary outcomes were represented by improved sedation at separation from parents, at induction of anesthesia, and reduction in postoperative agitation. Secondary outcomes were reduction in rescue analgesic drugs, and duration of surgery and anesthesia. Inclusion criteria were random allocation to treatment and comparison between dexmedetomidine and midazolam. Exclusion criteria were adult studies, duplicate publications, intravenous administration, and no data on main outcomes. Results: Data from 1033 children in 13 randomized trials were analyzed. Overall, in the dexmedetomidine group there was a higher incidence of satisfactory sedation at separation from parents (314 of 424 [74%] in the dex© 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 468–476
L. Pasin et al.
Dexmedetomidine vs midazolam in children
medetomidine group vs 196 of 391 [50%] in the midazolam group, RR = 1.30 [1.05–1.62], P = 0.02), a reduced incidence of postoperative agitation (14 of 140 [10%] vs 56 of 141 [40%], RR = 0.31 [0.13–0.73], P = 0.008), and a significant reduction in the rescue doses of analgesic drugs (49 of 241 [20%] vs 95 of 243 [39%], RR = 0.52 [0.39–0.70], P < 0.001). There was no evidence of a higher incidence of satisfactory sedation at anesthesia induction or any reduction of duration of surgery and anesthesia. Conclusions: Dexmedetomidine is effective in decreasing anxiety upon separation from parents, decreasing postoperative agitation, and providing more effective postoperative analgesia when compared with midazolam.
Introduction The preoperative period is a stressing occurrence for most patients undergoing surgery, especially children. It is estimated that 50–75% of children undergoing surgery will develop great anguish and anxiety throughout the whole perioperative period (1). Premedication is commonly used to reduce preoperative anxiety, to facilitate separation from parents, and to promote acceptance of mask induction. Among the different goals that can be achieved with premedication, the primary objective in children is anxiolysis. Premedication that effectively calms the child also minimizes parental anxiety (2,3). Benzodiazepines, and midazolam in particular, are the most frequently used premedications in pediatric patients (3–5). Efficacy of midazolam premedication in children has been widely demonstrated. However, in light of recent findings and pharmacological improvements, it should no longer be considered the drug of choice for pediatric premedication. In fact, Stewart et al. (6) showed that midazolam maintains implicit memory for potentially perioperative stressful events (e.g., mask induction) but induces scarce explicit memory for the same events. Accordingly, children premedicated with midazolam might unconsciously remember these potentially stressful events without being able to pull them consciously to mind, to elaborate, and make sense of them. Moreover midazolam, when compared to other drugs, resulted in ineffective prevention of emergence agitation and delirium in children (7). Therefore, different drugs like the a2-agonists have gained importance as alternatives for premedication in pediatric anesthesia. Dexmedetomidine is a highly selective a2-agonist with both analgesic and sedative effects. It produces a type of sedation recognized as ‘cooperative’ or ‘arousable’, which is different from the ‘clouding of consciousness’ sedation induced by drugs acting on the GABA system (8). These characteristics make it potentially useful for anesthesia premedication in children. © 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 468–476
A meta-analysis of all RCTs on dexmedetomidine versus midazolam was performed to evaluate dexmedetomidine perioperative sedative effects as a preanesthetic medication in children. Methods Search strategy Relevant studies were individually searched in PubMed, BioMedCentral, Embase, and the Cochrane Central Register of clinical trials (updated August 15th, 2014) by four expert investigators. Full PubMed search strategy aimed to include any randomized study ever performed in children with dexmedetomidine compared to midazolam in any clinical setting. Moreover, backward snowballing (scanning of references of relevant reviews and cited articles) was conducted, and international experts were contacted for additional studies. The database search was supplemented by online searching (e.g., Google), congress abstracts, and trial registers. No language restriction was imposed. Study selection References obtained from database and literature searches were first independently examined at a title/ abstract level by four investigators, with divergences resolved by consensus, and then, if potentially pertinent, the manuscripts were retrieved. Inclusion criteria were pediatric patients and random allocation to treatment (dexmedetomidine versus midazolam with no restrictions on dose or time of administration). Exclusion criteria included intravenous administration, adult patients, and lack of data on at least one of the following endpoints: sedation at separation from parents, sedation at anesthesia induction, number of children requiring supplemental postoperative analgesia, and safety. Two investigators independently assessed compliance to selection criteria and selected studies for the final analysis, with divergences finally resolved by consensus. 469
L. Pasin et al.
Dexmedetomidine vs midazolam in children
Data abstraction and study Baseline, procedural, and outcome data were independently abstracted by four trained investigators, with divergences resolved by consensus. Specifically, potential sources of significant heterogeneity, such as study design, sample size, route of administration, dose and timing, control treatment, as well as primary study endpoints, and other key outcomes were extracted. At least two separate attempts at contacting original authors were made in cases of missing data. Co-primary endpoints of the present meta-analysis were as follows: improved sedation at separation from parents, improved sedation at induction of anesthesia, and reduction in incidence of postoperative agitation. The secondary endpoints were reduction in rescue analgesic drugs and reduction in duration of surgery and anesthesia. Duration of surgery and anesthesia were defined as per authors’ definition. Adverse effects (hypotension, laryngospasm, shivering, bradycardia, nausea, and vomiting) were also analyzed. Internal validity and risk of bias assessment The internal validity and risk of bias of included trials was appraised by two independent reviewers according to the Cochrane Collaboration methods (9), with divergences resolved by consensus. Publication bias was assessed by visually inspecting funnel plots. Data analysis and synthesis Computations were performed with Review Manager version 5.2 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen). The hypothesis of statistical heterogeneity was tested by means of Cochran Q test, with statistical significance set at the two-tailed 0.10 level, whereas the extent of statistical consistency was measured with I2, defined as 100% 9 (Q-df)/Q, where Q is Cochran’s heterogeneity statistic and df, the degrees of freedom. Binary outcomes were analyzed to compute the individual and pooled risk ratio (RR) with 95% confidence intervals (CI), by means of the same models just described. Binary outcomes from individual studies were analyzed to compute individual and pooled risk ratio (RR) with 95% CIs, by means of inverse variance method and with a fixed effect model in case of low statistical inconsistency (I2 < 25%) or with random effect model (which better accommodates clinical and statistical variations) in case of moderate or high statistical inconsistency (I2 > 25%). Mean differences (MD) and 95% CIs were 470
computed for continuous variables using the same models as described. Sensitivity analyses were performed by sequentially removing each study and reanalysing the remaining dataset (producing a new analysis for each study removed) and by analysing only data from studies with low risk of bias. Statistical significance was set at the twotailed 0.05 level for hypothesis testing. Unadjusted P values are reported throughout. This study was performed in compliance with The Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (9–12). Results Study characteristics Database searches, snowballing, and contacts with experts yielded a total of 890 articles. Excluding 869 nonpertinent titles or abstracts, 21 studies were retrieved in completed form and were assessed according to the selection criteria (Figure 1). Eight studies were further excluded because of our prespecified exclusion criteria: one study was excluded because it was not randomized (Supplemental Reference 1), and seven because the control group did not receive midazolam as comparator drug (Supplemental References 2–8). The 13 included manuscripts randomized 1033 patients (531 to dexmedetomidine and 502 to midazolam) (Table 1) (13–25). Clinical heterogeneity was mostly due to type of surgery, route, dosage, and timing of drug administration (Table 1). Different routes of dexmedetomidine administration were used: intranasal in nine trials (13,14,16,17,21–25), oral in three trials (15,18,19), and sublingual in one trial (20).
Figure 1 Flow diagram for selection of articles. © 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 468–476
© 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 468–476
Strabismus surgery
2008
Dental restoration and/or extractions. Esophageal dilatation
2011
2007
Schmidt (21) Sheta (22)
2009
2008
Talon (24)
Yuen (25)
Elective reconstructive surgery Elective minor surgery
Elective full mouth rehabilitation.
32
50
50
64
45
36
22
50
25
19
32
56
30
60
45
45
36
20
50
25
22
32
52
30
60
45
Midazolam patients
1
1
1
1
1
1
1
1
1
1
1
1
0.5–1 mcgkg
2 mcgkg
1 mcgkg
1 mcgkg
1 mcgkg
1.5 mcgkg
2.5 mcgkg
4 mcgkg
1 mcgkg
1 mcgkg
3 mcgkg
1 mcgkg
1 mcgkg
Dex dose
1
0.5 mgkg
0.5 mgkg
0.2 mgkg
0.2 mgkg
0.5 mgkg
0.25 mgkg
0.5 mgkg
0.5 mgkg
0.2 mgkg
0.5 mgkg
0.5 mgkg
0.5 mgkg
0.2 mgkg
Midazolam dose
1
1
1
1
1
1
1
1
1
1
1
1
1
Intranasal
Intranasal
Intranasal
Intranasal
Intranasal
Sublingual
Oral
Oral
Intranasal
Intranasal
Oral
Intranasal
Intranasal
Route of administration dex
Oral
Oral
Intranasal
Intranasal
Oral
Sublingual
Oral
Oral
Intranasal
Oral
Oral
Oral
Intranasal
Route of administration midazolam
30–40 min before induction 60 min before induction
45 min before surgery 45–60 min before induction 60 min before surgery
30 min before induction 30 min before surgery 40–45 min before induction 45 min before induction
60 min before induction
45–60 min before induction 60 min before induction 60 min before induction
Timing administration dex
30 min before surgery 45–60 min before induction 60 min before surgery 30–40 min before induction 30 min before induction
30 min before induction 30 min before surgery 40–45 min before induction 20 min before induction
60 min before induction
45–60 min before induction 30 min before induction 60 min before induction
Timing administration midazolam
4–point scale
4–point scale
4–point scale
4–point scale
STAIC
4–point scale
n.a.
4–point scale PSAS; PAEDS
mYPAS
Modified OPS
mYPAS
4–point scale
Scale used for anxiety measurement
MOAA/S
Ramsey–like 4–point scale
6–point scale
4–point scale
4–point scale
MOAA/S
EAS
4 point sedation scale MAS
Modified Vancouver sedative recovery scale n.a.
MOAA/S
MOAA/S
Scale used for sedation measurement
Dex: Dexmedetomidine; MOAA/S: 6–point sedation scale, modified from the observer assessment of alertness and sedation scale; mYPAS: modified Yale preoperative anxiety scale; OPS: Objective Pain Scale; n.a: not available; PSAS: Parental Separation Anxiety Scale; MAS: Mask Acceptance Scale; PAEDS: Pediatric Anesthesia Emergence Delirium Scale; EAS: emergence agitation scale; STAIC: State–Trait Anxiety Inventory for Children.
2011
Sundaram (23)
2013
2013
Inguinal hernia repair, orchidopexy or circumcision Elective ambulatory surgical procedures Complete dental rehabilitation
Bone marrow biopsy
2014
2011
Elective surgery
2014
Pant (20)
Linares Segovia (16) Mostafa (17) Mountain (18) Ozcengiz (19)
Adenotonsillectomy
2011
Ghali (14) Kamal (15)
Adenotonsillectomy
2012
Akin (13)
Type of surgery
Year
First author
Dex patients
Table 1 Description of the 13 trials included in the meta–analysis
L. Pasin et al. Dexmedetomidine vs midazolam in children
471
Dexmedetomidine vs midazolam in children
Dexmedetomidine was administered at different dosages: Sensitivity (including only low risk of bias studies) >Small study effect (fixed model) Secondary endpoints Patients requiring rescue doses of postoperative analgesics >Sensitivity (including only low risk of bias studies) >Small study effect (random model) Duration of anesthesia (minutes) Duration of surgery (minutes)
Outcome
Table 2 Primary and secondary outcomes and sensitivity analyses
0.02 0.04 0.06 0.008 0.02
REVIEW ARTICLE
Dexmedetomidine vs midazolam as preanesthetic medication in children: a meta-analysis of randomized controlled trials Laura Pasin1, Daniela Febres1, Valentina Testa1, Elena Frati1, Giovanni Borghi1, Giovanni Landoni1,2 & Alberto Zangrillo1,2 1 Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy 2 Vita-Salute San Raffaele University, Milan, Italy
What’s known
• Premedication reduces perioperative anxiety in children. What this article adds
• Dexmedetomidine is more effective than midazolam in decreasing preoperative anxiety, postoperative agitation, and in providing more effective postoperative analgesia.
Implications
• Dexmedetomidine is an effective alternate sedative for pre medication in children
Keywords anesthesia-pediatric; dexmedetomidine; meta-analysis; midazolam; premedication; children Correspondence Dott. Laura Pasin, Department of Anaesthesia and Intensive Care, San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy Email: [email protected] Section Editor: Andrew Davidson Accepted 30 October 2014 doi:10.1111/pan.12587
468
Summary Introduction: The preoperative period is a stressing occurrence for most people undergoing surgery, in particular children. Approximately 50–75% of children undergoing surgery develop anxiety which is associated with distress on emergence from anesthesia and with later postoperative behavioral problems. Premedication, commonly performed with benzodiazepines, reduces preoperative anxiety, facilitates separation from parents, and promotes acceptance of mask induction. Dexmedetomidine is a highly selective a2-agonist with sedative and analgesic properties. A meta-analysis of all randomized controlled trials (RCTs) on dexmedetomidine versus midazolam was performed to evaluate its efficacy in improving perioperative sedation and analgesia, and in reducing postoperative agitation when used as a preanesthetic medication in children. Methods: Studies were independently searched in PubMed, BioMedCentral, Embase, and the Cochrane Central Register of clinical trials and updated on August 15th, 2014. Primary outcomes were represented by improved sedation at separation from parents, at induction of anesthesia, and reduction in postoperative agitation. Secondary outcomes were reduction in rescue analgesic drugs, and duration of surgery and anesthesia. Inclusion criteria were random allocation to treatment and comparison between dexmedetomidine and midazolam. Exclusion criteria were adult studies, duplicate publications, intravenous administration, and no data on main outcomes. Results: Data from 1033 children in 13 randomized trials were analyzed. Overall, in the dexmedetomidine group there was a higher incidence of satisfactory sedation at separation from parents (314 of 424 [74%] in the dex© 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 468–476
L. Pasin et al.
Dexmedetomidine vs midazolam in children
medetomidine group vs 196 of 391 [50%] in the midazolam group, RR = 1.30 [1.05–1.62], P = 0.02), a reduced incidence of postoperative agitation (14 of 140 [10%] vs 56 of 141 [40%], RR = 0.31 [0.13–0.73], P = 0.008), and a significant reduction in the rescue doses of analgesic drugs (49 of 241 [20%] vs 95 of 243 [39%], RR = 0.52 [0.39–0.70], P < 0.001). There was no evidence of a higher incidence of satisfactory sedation at anesthesia induction or any reduction of duration of surgery and anesthesia. Conclusions: Dexmedetomidine is effective in decreasing anxiety upon separation from parents, decreasing postoperative agitation, and providing more effective postoperative analgesia when compared with midazolam.
Introduction The preoperative period is a stressing occurrence for most patients undergoing surgery, especially children. It is estimated that 50–75% of children undergoing surgery will develop great anguish and anxiety throughout the whole perioperative period (1). Premedication is commonly used to reduce preoperative anxiety, to facilitate separation from parents, and to promote acceptance of mask induction. Among the different goals that can be achieved with premedication, the primary objective in children is anxiolysis. Premedication that effectively calms the child also minimizes parental anxiety (2,3). Benzodiazepines, and midazolam in particular, are the most frequently used premedications in pediatric patients (3–5). Efficacy of midazolam premedication in children has been widely demonstrated. However, in light of recent findings and pharmacological improvements, it should no longer be considered the drug of choice for pediatric premedication. In fact, Stewart et al. (6) showed that midazolam maintains implicit memory for potentially perioperative stressful events (e.g., mask induction) but induces scarce explicit memory for the same events. Accordingly, children premedicated with midazolam might unconsciously remember these potentially stressful events without being able to pull them consciously to mind, to elaborate, and make sense of them. Moreover midazolam, when compared to other drugs, resulted in ineffective prevention of emergence agitation and delirium in children (7). Therefore, different drugs like the a2-agonists have gained importance as alternatives for premedication in pediatric anesthesia. Dexmedetomidine is a highly selective a2-agonist with both analgesic and sedative effects. It produces a type of sedation recognized as ‘cooperative’ or ‘arousable’, which is different from the ‘clouding of consciousness’ sedation induced by drugs acting on the GABA system (8). These characteristics make it potentially useful for anesthesia premedication in children. © 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 468–476
A meta-analysis of all RCTs on dexmedetomidine versus midazolam was performed to evaluate dexmedetomidine perioperative sedative effects as a preanesthetic medication in children. Methods Search strategy Relevant studies were individually searched in PubMed, BioMedCentral, Embase, and the Cochrane Central Register of clinical trials (updated August 15th, 2014) by four expert investigators. Full PubMed search strategy aimed to include any randomized study ever performed in children with dexmedetomidine compared to midazolam in any clinical setting. Moreover, backward snowballing (scanning of references of relevant reviews and cited articles) was conducted, and international experts were contacted for additional studies. The database search was supplemented by online searching (e.g., Google), congress abstracts, and trial registers. No language restriction was imposed. Study selection References obtained from database and literature searches were first independently examined at a title/ abstract level by four investigators, with divergences resolved by consensus, and then, if potentially pertinent, the manuscripts were retrieved. Inclusion criteria were pediatric patients and random allocation to treatment (dexmedetomidine versus midazolam with no restrictions on dose or time of administration). Exclusion criteria included intravenous administration, adult patients, and lack of data on at least one of the following endpoints: sedation at separation from parents, sedation at anesthesia induction, number of children requiring supplemental postoperative analgesia, and safety. Two investigators independently assessed compliance to selection criteria and selected studies for the final analysis, with divergences finally resolved by consensus. 469
L. Pasin et al.
Dexmedetomidine vs midazolam in children
Data abstraction and study Baseline, procedural, and outcome data were independently abstracted by four trained investigators, with divergences resolved by consensus. Specifically, potential sources of significant heterogeneity, such as study design, sample size, route of administration, dose and timing, control treatment, as well as primary study endpoints, and other key outcomes were extracted. At least two separate attempts at contacting original authors were made in cases of missing data. Co-primary endpoints of the present meta-analysis were as follows: improved sedation at separation from parents, improved sedation at induction of anesthesia, and reduction in incidence of postoperative agitation. The secondary endpoints were reduction in rescue analgesic drugs and reduction in duration of surgery and anesthesia. Duration of surgery and anesthesia were defined as per authors’ definition. Adverse effects (hypotension, laryngospasm, shivering, bradycardia, nausea, and vomiting) were also analyzed. Internal validity and risk of bias assessment The internal validity and risk of bias of included trials was appraised by two independent reviewers according to the Cochrane Collaboration methods (9), with divergences resolved by consensus. Publication bias was assessed by visually inspecting funnel plots. Data analysis and synthesis Computations were performed with Review Manager version 5.2 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen). The hypothesis of statistical heterogeneity was tested by means of Cochran Q test, with statistical significance set at the two-tailed 0.10 level, whereas the extent of statistical consistency was measured with I2, defined as 100% 9 (Q-df)/Q, where Q is Cochran’s heterogeneity statistic and df, the degrees of freedom. Binary outcomes were analyzed to compute the individual and pooled risk ratio (RR) with 95% confidence intervals (CI), by means of the same models just described. Binary outcomes from individual studies were analyzed to compute individual and pooled risk ratio (RR) with 95% CIs, by means of inverse variance method and with a fixed effect model in case of low statistical inconsistency (I2 < 25%) or with random effect model (which better accommodates clinical and statistical variations) in case of moderate or high statistical inconsistency (I2 > 25%). Mean differences (MD) and 95% CIs were 470
computed for continuous variables using the same models as described. Sensitivity analyses were performed by sequentially removing each study and reanalysing the remaining dataset (producing a new analysis for each study removed) and by analysing only data from studies with low risk of bias. Statistical significance was set at the twotailed 0.05 level for hypothesis testing. Unadjusted P values are reported throughout. This study was performed in compliance with The Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (9–12). Results Study characteristics Database searches, snowballing, and contacts with experts yielded a total of 890 articles. Excluding 869 nonpertinent titles or abstracts, 21 studies were retrieved in completed form and were assessed according to the selection criteria (Figure 1). Eight studies were further excluded because of our prespecified exclusion criteria: one study was excluded because it was not randomized (Supplemental Reference 1), and seven because the control group did not receive midazolam as comparator drug (Supplemental References 2–8). The 13 included manuscripts randomized 1033 patients (531 to dexmedetomidine and 502 to midazolam) (Table 1) (13–25). Clinical heterogeneity was mostly due to type of surgery, route, dosage, and timing of drug administration (Table 1). Different routes of dexmedetomidine administration were used: intranasal in nine trials (13,14,16,17,21–25), oral in three trials (15,18,19), and sublingual in one trial (20).
Figure 1 Flow diagram for selection of articles. © 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 468–476
© 2015 John Wiley & Sons Ltd Pediatric Anesthesia 25 (2015) 468–476
Strabismus surgery
2008
Dental restoration and/or extractions. Esophageal dilatation
2011
2007
Schmidt (21) Sheta (22)
2009
2008
Talon (24)
Yuen (25)
Elective reconstructive surgery Elective minor surgery
Elective full mouth rehabilitation.
32
50
50
64
45
36
22
50
25
19
32
56
30
60
45
45
36
20
50
25
22
32
52
30
60
45
Midazolam patients
1
1
1
1
1
1
1
1
1
1
1
1
0.5–1 mcgkg
2 mcgkg
1 mcgkg
1 mcgkg
1 mcgkg
1.5 mcgkg
2.5 mcgkg
4 mcgkg
1 mcgkg
1 mcgkg
3 mcgkg
1 mcgkg
1 mcgkg
Dex dose
1
0.5 mgkg
0.5 mgkg
0.2 mgkg
0.2 mgkg
0.5 mgkg
0.25 mgkg
0.5 mgkg
0.5 mgkg
0.2 mgkg
0.5 mgkg
0.5 mgkg
0.5 mgkg
0.2 mgkg
Midazolam dose
1
1
1
1
1
1
1
1
1
1
1
1
1
Intranasal
Intranasal
Intranasal
Intranasal
Intranasal
Sublingual
Oral
Oral
Intranasal
Intranasal
Oral
Intranasal
Intranasal
Route of administration dex
Oral
Oral
Intranasal
Intranasal
Oral
Sublingual
Oral
Oral
Intranasal
Oral
Oral
Oral
Intranasal
Route of administration midazolam
30–40 min before induction 60 min before induction
45 min before surgery 45–60 min before induction 60 min before surgery
30 min before induction 30 min before surgery 40–45 min before induction 45 min before induction
60 min before induction
45–60 min before induction 60 min before induction 60 min before induction
Timing administration dex
30 min before surgery 45–60 min before induction 60 min before surgery 30–40 min before induction 30 min before induction
30 min before induction 30 min before surgery 40–45 min before induction 20 min before induction
60 min before induction
45–60 min before induction 30 min before induction 60 min before induction
Timing administration midazolam
4–point scale
4–point scale
4–point scale
4–point scale
STAIC
4–point scale
n.a.
4–point scale PSAS; PAEDS
mYPAS
Modified OPS
mYPAS
4–point scale
Scale used for anxiety measurement
MOAA/S
Ramsey–like 4–point scale
6–point scale
4–point scale
4–point scale
MOAA/S
EAS
4 point sedation scale MAS
Modified Vancouver sedative recovery scale n.a.
MOAA/S
MOAA/S
Scale used for sedation measurement
Dex: Dexmedetomidine; MOAA/S: 6–point sedation scale, modified from the observer assessment of alertness and sedation scale; mYPAS: modified Yale preoperative anxiety scale; OPS: Objective Pain Scale; n.a: not available; PSAS: Parental Separation Anxiety Scale; MAS: Mask Acceptance Scale; PAEDS: Pediatric Anesthesia Emergence Delirium Scale; EAS: emergence agitation scale; STAIC: State–Trait Anxiety Inventory for Children.
2011
Sundaram (23)
2013
2013
Inguinal hernia repair, orchidopexy or circumcision Elective ambulatory surgical procedures Complete dental rehabilitation
Bone marrow biopsy
2014
2011
Elective surgery
2014
Pant (20)
Linares Segovia (16) Mostafa (17) Mountain (18) Ozcengiz (19)
Adenotonsillectomy
2011
Ghali (14) Kamal (15)
Adenotonsillectomy
2012
Akin (13)
Type of surgery
Year
First author
Dex patients
Table 1 Description of the 13 trials included in the meta–analysis
L. Pasin et al. Dexmedetomidine vs midazolam in children
471
Dexmedetomidine vs midazolam in children
Dexmedetomidine was administered at different dosages: Sensitivity (including only low risk of bias studies) >Small study effect (fixed model) Secondary endpoints Patients requiring rescue doses of postoperative analgesics >Sensitivity (including only low risk of bias studies) >Small study effect (random model) Duration of anesthesia (minutes) Duration of surgery (minutes)
Outcome
Table 2 Primary and secondary outcomes and sensitivity analyses
0.02 0.04 0.06 0.008 0.02
